2. Academic Validation
  3. A prenatally diagnosed case of Meckel-Gruber syndrome with novel compound heterozygous pathogenic variants in the TXNDC15 gene

A prenatally diagnosed case of Meckel-Gruber syndrome with novel compound heterozygous pathogenic variants in the TXNDC15 gene

  • Mol Genet Genomic Med. 2019 May;7(5):e614. doi: 10.1002/mgg3.614.
Konstantin Ridnõi 1 2,  Marek Šois 3,  Eve Vaidla 4,  Sander Pajusalu 4 5,  Larissa Kelder 6,  Tiia Reimand 4 7,  Katrin Õunap 2 4
Affiliations

Affiliations

  • 1 Centre for Perinatal Care, Women's Clinic, East-Tallinn Central Hospital, Tallinn, Estonia.
  • 2 Department of Clinical Genetics, Institute of Clinical Medicine, University of Tartu, Tartu, Estonia.
  • 3 Fetal Ultrasound Screening Centre, Tallinn, Estonia.
  • 4 United Laboratories, Department of Clinical Genetics, Tartu University Hospital, Tartu, Estonia.
  • 5 Department of Genetics, Yale University School of Medicine, New Haven, Connecticut.
  • 6 Centre of Pathology, Diagnostic Clinic, East-Tallinn Central Hospital, Tallinn, Estonia.
  • 7 Department of Biomedicine, Institute of Biomedicine and Translational Medicine, University of Tartu, Tartu, Estonia.
PMID: 30851085 DOI: 10.1002/mgg3.614
Abstract

Background: Meckel-Gruber syndrome (MKS) is a well-known rare disease that can be detected on prenatal ultrasound. Meckel-Gruber syndrome has very heterogeneous etiology; at least, 17 genes have been described in association with MKS. The characteristic findings in fetuses affected by MKS are encephalocele (usually occipital), postaxial polydactyly, and polycystic dysplastic kidneys. However, the association of the TXNDC15 gene with MKS has been reported only once before in three consanguineous families.

Methods: We report a new case of MKS diagnosed at 12 + 1 weeks of gestation with typical ultrasound findings, but with novel compound heterozygous pathogenic variants in the TXNDC15 gene identified by whole-exome Sequencing (WES).

Results: This is the second clinical report supporting TXNDC15 as a novel causative gene of MKS, and the first describing a case in a non-consanguineous family with causative compound heterozygous mutations.

Conclusions: Meckel-Gruber syndrome is a very heterogeneous syndrome in terms of the associated causal genes. In the first-line diagnosis, we used an next-generation Sequencing (NGS)-based large gene panel, but only 10 MKS genes were available on the platform used. In the case of prenatal ultrasound findings that are highly suggestive of MKS and a negative NGS MKS gene panel, WES should also be performed to not miss rare gene associations.

Keywords

Meckel-Gruber syndrome; TXNDC15 gene; ciliopathies; fetal ultrasound; prenatal.

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